GARDASIL®: Prophylactic Human Papillomavirus Vaccine Development – From Bench Top to Bed-side

Shi, Li; Sings, Heather L.; Bryan, Janine T.; Wang, B; Wang, Y; Mach, H.; Kosinski, Michael; Washabaugh, Michael W.; Sitrin, Robert D.; Barr, Eliav

doi:10.1038/sj.clpt.6100055

Cited by 114 publications

(79 citation statements)

References 15 publications

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“…An effective prophylactic vaccine, Gardasil, approved for clinical use has shown a remarkable degree of protection [2,3]. However, this vaccine is not expected to eliminate preexisting HPV disease.…”

Section: Introductionmentioning

confidence: 99%

Protective immunity with an E1 multivalent epitope DNA vaccine against cottontail rabbit papillomavirus (CRPV) infection in an HLA-A2.1 transgenic rabbit model

Cladel

Peng

et al. 2008

Vaccine

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Cottontail rabbit papillomavirus (CRPV)/rabbit model is widely used to study pathogenesis of papillomavirus infections and malignant tumor progression. Recently, we established HLA-A2.1 transgenic rabbit lines and demonstrated efficacy for the testing of immunogenicity of a well-known A2-resticted epitope (HPV16E7/82-90) [1]. In the present study, we screened five HLA-A2.1 restricted epitopes from CRPV E1 (selected using online MHCI epitope prediction software) and constructed a multivalent epitope DNA vaccine (CRPVE1ep1-5). CRPVE1ep1-5 and a control DNA vaccine (Ub3) were then delivered intracutaneously onto normal and HLA-A2.1 transgenic rabbits respectively by a helium-driven gene-gun delivery system. One, two or three immunizations were given to different groups of animals from both New Zealand White outbred and EIII/JC inbred genetic background. Two and three immunizations with CRPVE1ep1-5 DNA vaccine provided complete protection against viral DNA infection of HLA-A2.1 transgenic rabbits from both genetic backgrounds but not in the control vaccinated groups. One immunization, however, failed to protect HLA-A2.1 transgenic rabbits against viral DNA infection. This study further demonstrated that the HLA-A2.1 transgenic rabbits can be used to test the immunogenicity of HLA-A2.1 restricted epitopes identified by MHCI epitope predication software.

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Section: Introductionmentioning

confidence: 99%

Protective immunity with an E1 multivalent epitope DNA vaccine against cottontail rabbit papillomavirus (CRPV) infection in an HLA-A2.1 transgenic rabbit model

Cladel

Peng

et al. 2008

Vaccine

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“…For each type, we tested intact VLPs and disrupted VLPs to determine if the MAbs could discriminate between the two. This is an important criterion for product release and clinical assays, as intact VLPs have been shown to and are expected to be stable and closely model the HPV virions (17,18).…”

Section: Resultsmentioning

confidence: 99%

“…Immulon 4B microtiter plates were coated with VLP antigens of different HPV types under intact or disrupted conditions. Intact VLPs for types 6,11,16,18,31,33,45,52, and 58 were solubilized in 50 mM histidine, 0.5 M NaCl, pH 6.2, and incubated overnight at 2 to 8°C. VLPs were disrupted by incubation in 0.2 M sodium carbonate buffer, pH 10.6, with 10 mM dithiothreitol (DTT) and dried on the plates overnight at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Development of Neutralizing Monoclonal Antibodies for Oncogenic Human Papillomavirus Types 31, 33, 45, 52, and 58

Brown

Seitz

Towne

et al. 2014

Clin Vaccine Immunol

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bHuman papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and type specific and recognized conformation-dependent neutralizing epitopes. Such characteristics make these antibodies useful tools for monitoring the production and potency of a prototype vaccine as well as monitoring vaccine-induced immune responses in the clinic. This major capsid protein self-assembles into virus-like particles (VLPs) that mimic the structure of the native virion (2, 3). The two currently licensed vaccines offer protection against HPV types 16 and 18, which account for 70% of cervical cancer cases (4); the quadrivalent vaccine also offers protection against HPV types 6 and 11, which account for 90% of genital warts (5). A second-generation HPV vaccine was developed by Merck to provide extended coverage for the next five most prevalent oncogenic HPV types: 31, 33, 45, 52, and 58. Inclusion of VLPs to the additional five oncogenic HPV types will potentially increase the coverage to approximately 90% (4).Monitoring HPV type-specific neutralizing epitopes is an essential aspect of the development of this vaccine. A meaningful and rapid evaluation of serological responses facilitates decisions regarding the optimum vaccine and assists the collection of data for regulatory approval. Potency assays conducted in vivo (typically mouse potency assays) and functional in vitro assays such as pseudovirus and plaque assays can be laborious and difficult to standardize. Assays that utilize antibody binding and competition can act as valuable surrogates and can be readily qualified and adapted for high-throughput and automated platforms (6, 7). A critical requirement is that the antibodies that are chosen for the assays reflect the biological properties of the original potency and neutralization assays (8).Neutralizing antibodies to HPV L1 VLPs are primarily type specific (9) and bind to surface-exposed conformational loops (10). Despite high degrees of L1 sequence homology among members of the same family, neutralizing antibodies to cross-reactive epitopes have rarely been identified (11). Panels of monoclonal antibodies (MAbs) have be...

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“…In diesem Fall konnten mittels genetischer Modifikationen nicht-infektiöse homologe Hepatitis-B-Virus-Partikel hergestellt werden, die dem Immunsystem bei Impfung die entscheidenden Antigene darbieten. Ein weiteres Paradebeispiel für einen rekombinanten Impfstoff ist der gegen Humane Papillomaviren (HPV), die Genitalwarzen hervorrufen und Gebärmutter-halskrebs auslösen können [29]. Eine Variante solcher Impfstoffe nutzt heterologe Viruspartikel als Vektorsysteme für die schützenden Antigene des Erregers (zum Beispiel die ChimeriVax TM -Impfstoffe).…”

Section: Tab 4 Humane Immunglobulineunclassified

Neue Impfstoffkonzepte auf Basis moderner Erkenntnisse der Immunologie

Kaufmann

Meinke

Gabain

2009

Bundesgesundheitsbl.

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GARDASIL®: Prophylactic Human Papillomavirus Vaccine Development – From Bench Top to Bed-side

Cited by 114 publications

References 15 publications

Protective immunity with an E1 multivalent epitope DNA vaccine against cottontail rabbit papillomavirus (CRPV) infection in an HLA-A2.1 transgenic rabbit model

Protective immunity with an E1 multivalent epitope DNA vaccine against cottontail rabbit papillomavirus (CRPV) infection in an HLA-A2.1 transgenic rabbit model

Development of Neutralizing Monoclonal Antibodies for Oncogenic Human Papillomavirus Types 31, 33, 45, 52, and 58

Neue Impfstoffkonzepte auf Basis moderner Erkenntnisse der Immunologie

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